Thrombopoietin is a cytokine consisting of 332 amino acids that increases platelet production by stimulating differentiation and proliferation of hematopoietic stem cells, megakaryocytic progenitor cells and megakaryocytes mediated by its receptor and therefore is promising as a drug for hematological disorders. Recent reports that it stimulates differentiation and proliferation of vascular endothelial cells and endothelial progenitor cells have raised expectations of therapeutic angiogenesis, anti-arteriosclerosis and prevention of cardiovascular events (for example, non-patent document 1, non-patent document 2 and non-patent document 3).
Biologically active substances which have been known so far to regulate platelet production through the thrombopoietin receptor include, in addition to thrombopoietin itself, low molecular weight peptides having affinity for the thrombopoietin receptor (for example, patent document 1, patent document 2, patent document 3 and patent document 4).
As a result of search for nonpeptidic low molecular weight compounds that increase platelet production mediated by the thrombopoietin receptor, low molecular weight compounds having affinity for the thrombopoietin receptor have been reported (for example, patent document 5 to patent document 27).    Patent document 1: JP-A-10-72492    Patent document 2: WO96/40750    Patent document 3: WO96/40189    Patent document 4: WO98/25965    Patent document 5: JP-A-11-1477    Patent document 6: JP-A-11-152276    Patent document 7: WO01/07423    Patent document 8: WO01/53267    Patent document 9: WO02/059099    Patent document 10: WO02/059100    Patent document 11: WO00/35446    Patent document 12: WO00/66112    Patent document 13: WO01/34585    Patent document 14: WO01/17349    Patent document 15: WO01/39773    Patent document 16: WO01/21180    Patent document 17: WO01/89457    Patent document 18: WO02/49413    Patent document 19: WO02/085343    Patent document 20: WO03/103686    Patent document 21: JP-A-2001-97948    Patent document 22: WO99/11262    Patent document 23: WO02/062775    Patent document 24: WO03/062233    Patent document 25 JP-A-2003-238565    Patent document 26: WO04/033433    Patent document 27: WO04/108683    Non-patent document 1: Microvasc. Res., 1999: 58, p. 108-113    Non-patent document 2: Circ. Res., 1999: 84, p. 785-796    Non-patent document 3: Blood 2001:98, p. 71a-72a